Proper biomechanical function of cartilage is determined by the structure and mechanical characteristics of its extracellular matrix (ECM) at the nanoscale. In osteoarthritis (OA), a chronic cartilage degenerative disease that affects more than 27 million Americans, changes of nanomechanical properties are direct manifestations of the breakdown and dysfunction of cartilage. To this end, understanding the structure and mechanical properties of cartilage ECM at the nanoscale has the potential to yield new targets for disease detection and treatment, as well as cartilage functional repair.

In this dissertation, nanomechanical properties of murine joint tissues were studied, with a focus on three aspects of biomechanical function and disease. Specifically, this study probed the early detection of knee OA, molecular mechanisms of cartilage development, as well as the structure-mechanics principles of a unique cartilaginous tissue pair, the temporomandibular joint (TMJ) disc and condyle cartilage. Atomic force microscopy (AFM)-based nanoindentation was used as the primary tool to assess the mechanical properties of micrometer-thick murine tissues, which cannot be studied via conventional biomechanical assays.

Outcomes of this dissertation underscored the high sensitivity of nanoindentation in detecting cartilage degeneration in OA, and the importance of two regulatory matrix molecules, decorin and biglycan, in cartilage function. Further, understanding of the TMJ disc and condyle cartilage biomechanics provided a benchmark for probing the pathogenesis of TMJ OA using murine models. Taken together, findings from this dissertation will contribute to building a fundamental knowledge basis of cartilage pathomechanics, which has the potential to yield new insights into new disease detection and tissue repair strategies.